POS1067 DOMAINS CONTRIBUTING TO MINIMAL DISEASE ACTIVITY ACHIEVEMENT IN PATIENTS WITH PSORIATIC ARTHRITIS RECEIVING GUSELKUMAB
Authors: L. Coates, P. Rahman, P. J. Mease, M. Shawi, E. Rampakakis, A. Kollmeier, X. L. Xu, S. D. Chakravarty, I. Mcinnes, L. S. Tam
Journal: Annals of the Rheumatic Diseases (2022)

Background Despite effective treatments, a minority of psoriatic arthritis (PsA) patients (pts) realize sustained minimal disease activity (MDA). 1 Pt-driven domains of MDA are less frequently achieved, potentially arising from comorbid conditions. 1 Objectives Identify domains contributing to and factors influencing MDA achievement in the 2-year Phase 3 DISCOVER-2 trial. Methods Randomized and treated adults (N=739) had active PsA, were biologic/JAK inhibitor-naive, and had swollen and tender joint counts (SJC/TJC) each ≥5 and C-reactive protein ≥0.6 mg/dL. Pts with medical history of fibromyalgia (FM) were not excluded. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. MDA requires fulfillment of ≥5/7 criteria: TJC ≤1, SJC ≤1, Psoriasis Area and Severity Index (PASI) score ≤1, Pt Pain score ≤15, Pt global disease activity (PtGA) score ≤20, Health Assessment Questionnaire – Disability Index (HAQ-DI) score ≤0.5, and ≤1 tender entheses. A longitudinal trajectory of achieving each MDA criterion through W100 was derived (nonresponder imputation [NRI]). Time to achieve was estimated via Kaplan-Meier survival curve for scores deriving from native scales and those normalized to a 0-66 scale (corresponding to SJC). Multivariate regression models for time to achievement (cox proportional hazard) and achievement (logistic regression) of MDA at W100 identified predictors of response. Results Among 492 GUS pts, continuous improvement across all MDA domains was shown through proportions of pts achieving criteria at W24 &amp; W100 (NRI): SJC (45% &amp; 65%), TJC (16% &amp; 34%), PASI (71% &amp; 72%), Pt Pain (23% &amp; 37%), PtGA (29% &amp; 45%), HAQ-DI (34% &amp; 44%), entheseal points (75% &amp; 80%). Times to achieve minimal SJC, PASI, and enthesitis with GUS were significantly faster than for PtGA, Pt Pain, TJC, and HAQ-DI for native-scale scores; when normalized, PtGA, Pt Pain, and HAQ-DI were achieved less often (Figure 1). Higher baseline (BL) Pt Pain score and lower BL Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (worse fatigue) were significant predictors of longer time; lower BMI was associated with shorter time to achieve Pt Pain ≤15. Results for achieving Pt Pain ≤15 at W100 were similar. Worse baseline fatigue and PtGA were significant predictors of longer time to PtGA ≤20; worse fatigue also predicted non-achievement of PtGA ≤20 at W100. For time to achieve HAQ-DI ≤0.5, significant BL negative predictors were higher age and BL HAQ-DI score, which were also significant predictors of HAQ-DI ≤0.5 non-achievement at W100. Although seen in only a small number of pts, a significant impact of FM history and suicidal ideation/behavior on Pt Pain ≤15 and HAQ-DI ≤0.5, respectively, was observed (Table 1). Table 1. Predictors of Time to Achievement and Achievement of Recalcitrant MDA Domains at Week 100 in GUS-randomized Pts (N=492 ) Time to achievement Independent BL Variables Pt Pain ≤15 PtGA ≤20 HAQ-DI ≤0.5 HR (95% CI) HR (95% CI) HR (95% CI) Age - 0.98 (0.97-0.99) † HAQ-DI - 0.26 (0.19-0.36) ‡ PtGA VAS - 0.99 (0.98-1.00) * - Pain VAS 0.99 (0.98-1.00) † - FACIT-Fatigue § 1.02 (1.00-1.03) * 1.02 (1.01-1.04) ‡ - BMI 0.98 (0.96-1.00) * FM (N=8) 0.70 (0.55-0.90) † - - Achievement at W100 OR (95% CL) ∥ OR (95% CL) ∥ OR (95% CL) ∥ Age - - 0.98 (0.96: 1.00) * HAQ-DI - - 0.13 (0.08: 0.20) ‡ Pain VAS 0.98 (0.97: 1.00) † - - FACIT-Fatigue § 1.02 (1.00: 1.05) * 1.05 (1.03: 1.07) ‡ - BMI 0.97 (0.94: 1.00) * - - Suicidal Ideation/Behaviour (N=9) - - 0.16 (0.03: 0.86) * FM (N=8) 0.59 (0.40: 0.86) † - - HR Hazard Ratio CI Confidence Interval OR Odds Ratio CL Confidence Limits * p &lt;0.05; † p &lt;0.01; ‡ p ≤0.0001 § Higher score indicates less fatigue ∥ Wald CL Conclusion GUS provided continuous improvement in each MDA domain through W100. BL domain score, as well as age, fatigue, and BMI, were significant determinants of MDA achievement in recalcitrant pt-driven domains (Pt Pain, PtGA, HAQ-DI). The impact of FM and mental health status merits further evaluation. References [1]Rahman et al. BMJ Open 2017;7(8): e016619 Disclosure of Interests Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC,, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly and Company, GSK, Janssen, Novartis, Roche, and UCB, Lai-Shan Tam Consultant of: Janssen, Pfizer, Sanofi, AbbVie, Boehringer Ingelheim, and Lilly, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis and Pfizer